An Alternative Method for Estimating Mutagenic Potency in BioAssays with Non-Linear Time Dependent Responses *

Michael J. Bauer and Andrew Reilly

Although there is extensive literature describing analyses associated with potency experiments, the bulk of it is confined to considering parallel line assays where responses are observed at differing concentrations. In contrast, the current investigation involves single concentration assays in which non-linear responses are observed over time. A literature search failed to identify an extant technique for estimating the mutagenic potency in temporal data of this type. We will present a procedure for summarizing the responses in terms of total mutagenicity by fitting and then integrating a time dependent polynomial model. The technique is applied in experiments measuring mutant frequencies (Mf) following acute exposure to high LET-irradiation. Mutations are observed at the HPRT locus of T-lymphocytes extracted from the spleens of mice necropsied at 0, 2, 4, and 8 weeks of exposure. A similar idea is employed in pharmacokinetic studies where drug absorption efficiency is measured via the area under the drug concentration versus time curve.